The overall goal of this proposal is the identification of new parameters which will allow the separation of breast cancer cases into predictable prognostic groupings. Analysis of survival patterns of breast cancer patients with local and regional diseases suggests two populations of patients with a striking difference in survival, with relative mortality rates of 2.5% and 25% per year, respectively. Our approach will include a retrospective immunohistochemical analysis of these two groups of breast cancer patients, including those surviving less than two and greater than ten years after mastectomy. The specific aims of the current proposal are to characterize retrospectively a series of primary breast cancers with regard to the expression of a profile of oncodevelopmental, hormonal and tissue specific markers, employing immunohistochemical methods. The immunoperoxidase technique of localizing tissue antigens permits the retrospective identification of tumor markers in tissue that has been routinely processed in the Pathology laboratory by formalin fixation and paraffin embedding. The profile of tumor marker expression will be correlated with survival patterns of patients, with standard morphologic prognostic parameters and, finally, with known epidemiologic risk factors. These studies have the potential of identifying new prognostic determinants that can delineate subsets of breast cancer patients at diagnosis who will have different survival subsequently. These data may help identify new subsets of patients who might benefit from post-operative adjuvant chemo- and radiotherapy programs, and to help guide design of future clinical trials and expand our understanding of the epidemiology and etiology of breast cancer.